GABA regulates the multidirectional tangential migration of GABAergic interneurons in living neonatal mice.
GABA regulates the multidirectional tangential migration of GABAergic interneurons in living neonatal mice.
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DOI：
10.1371/journal.pone.0027048
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Nabekura J
中科院分区：
文献类型：
--
作者：
Inada H;Watanabe M;Uchida T;Ishibashi H;Wake H;Nemoto T;Yanagawa Y;Fukuda A;Nabekura J
皮质GABA能中间神经元起源于神经节隆起，并在早期发育阶段切向迁移到皮质板。为了阐明GABA能中间神经元在活体动物中迁移的特征，我们建立了一个实验设计，专门用于用双光子激光扫描显微镜对新生小鼠新皮层进行体内延时成像。在囊泡GABA/甘氨酸转运体（VGAT）-Venus转基因小鼠从出生（P0）到P3，我们观察到多向切向迁移的遗传定义的GABA能中间神经元在新皮质边缘区。这种迁移的性质，如运动率（距离/小时），移动的方向，和迁移的神经元的比例，静止的神经元，并没有改变通过P0至P3，虽然在边缘区的GABA能神经元的密度随着年龄的增长而下降。因此，单个GABA能神经元的切向运动特性在发育过程中保持不变。GABAA受体和Na+-K+-Cl−协同转运蛋白的药理学阻断，以及螯合细胞内Ca 2+，都显著降低了体内运动率。新生VGAT-Venus转基因小鼠的运动速率和皮层内GABA含量显著高于GAD 67-GFP敲入小鼠，表明细胞外GABA浓度可促进多向切向迁移。事实上，应用于GAD 67-GFP小鼠的地西泮显著增加了运动率。在体外新皮层切片制备中，我们证实GABA在P0-P3诱导VGAT-Venus小鼠中GABA能中间神经元的NKCC敏感性去极化。因此，环境GABA对GABAAR的激活使GABA能中间神经元去极化，导致其体内多向运动的加速。
Cortical GABAergic interneurons originate from ganglionic eminences and tangentially migrate into the cortical plate at early developmental stages. To elucidate the characteristics of this migration of GABAergic interneurons in living animals, we established an experimental design specialized for in vivo time-lapse imaging of the neocortex of neonate mice with two-photon laser-scanning microscopy. In vesicular GABA/glycine transporter (VGAT)-Venus transgenic mice from birth (P0) through P3, we observed multidirectional tangential migration of genetically-defined GABAergic interneurons in the neocortical marginal zone. The properties of this migration, such as the motility rate (distance/hr), the direction moved, and the proportion of migrating neurons to stationary neurons, did not change through P0 to P3, although the density of GABAergic neurons at the marginal zone decreased with age. Thus, the characteristics of the tangential motility of individual GABAergic neurons remained constant in development. Pharmacological block of GABAA receptors and of the Na+-K+-Cl− cotransporters, and chelating intracellular Ca2+, all significantly reduced the motility rate in vivo. The motility rate and GABA content within the cortex of neonatal VGAT-Venus transgenic mice were significantly greater than those of GAD67-GFP knock-in mice, suggesting that extracellular GABA concentration could facilitate the multidirectional tangential migration. Indeed, diazepam applied to GAD67-GFP mice increased the motility rate substantially. In an in vitro neocortical slice preparation, we confirmed that GABA induced a NKCC sensitive depolarization of GABAergic interneurons in VGAT-Venus mice at P0-P3. Thus, activation of GABAAR by ambient GABA depolarizes GABAergic interneurons, leading to an acceleration of their multidirectional motility in vivo.
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影响因子：
2.5
作者：
LUHMANN, HJ;PRINCE, DA
通讯作者：
PRINCE, DA
影响因子：
2.9
作者：
Chowdhury TG;Jimenez JC;Bomar JM;Cruz-Martin A;Cantle JP;Portera-Cailliau C
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Portera-Cailliau C
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Ernfors, Patrik
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3.4
作者：
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通讯作者：
FAIREN, A
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5.5
作者：
EBIHARA, S;SHIRATO, K;AKAIKE, N
通讯作者：
AKAIKE, N